In silico exploration of 3d structures of pfmsp3 and pfmsp6 invasion genes and their allelic differences

Abstract

Malaria is one of the leading causes of child mortality in Africa. According to the World Health Organization report 2011, there was an estimated 655,000 deaths in 2010 in Africa most of which have been reported among children. This implies that malaria is a threat to the human population. One of the ways to deal with this problem is to develop effective vaccines against malaria. Antibody Dependent Cellular Inhibition (ADCI) is a phenomenon where individuals who have been exposed to malaria develop a form of immunity also known as premunition. The ADCI effect is effective against some Plasmodium falciparum invasion proteins such as Merozoite Surface Protein (MSP) 3 and 6 making them potential candidates for a malaria vaccine. This study was conducted to determine the 3D structures of MSP3 and MSP6 as well as determine the allelic differences between 3D7 and K1 strains. Due to the lack of good templates we resorted to use ab initio modeling which is only able to model very small proteins or peptides from larger ones. Smaller regions of interest such as high activity binding peptides, regions that have been shown to elicit inhibition in in vitro assays as well as epitopes were identified and modeled. For the regions modeled and verified to be correct, we were able to identify pockets that are potential protein-ligand interaction as well as antibody binding sites. This research will be useful to researchers focusing on malaria drugs and vaccines who need to know what type of ligands to design and which areas to target.